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Idiopathic Generalized Epilepsy (idiopathic + generalized_epilepsy)
Selected AbstractsWorkshop on Idiopathic Generalized Epilepsies: Bridging basic science and clinical research (October 3,6, 2007; Antalya, Turkey)EPILEPSIA, Issue 11 2008Edward H. Bertram First page of article [source] Idiopathic Generalized Epilepsies: A Review and Modern ApproachEPILEPSIA, Issue 2005Chrysostomos P. Panayiotopoulos M.D., Ph.D. First page of article [source] Historical Aspects of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Peter Wolf Summary:, Early in these proceedings, the origin of the three terms in the title, "idiopathic generalized epilepsy," is discussed with respect to their significance over time, and typical misunderstandings. In the mid-20th century, a rather chaotic use of a multitude of often loosely defined terms had developed, which increasingly became an obstacle to a meaningful international discussion. The International League against Epilepsy (ILAE) took the initiative to develop an internationally accepted terminology with a classification system consisting of a classification of seizures (1981) and a classification of syndromes (1989). The Idiopathic Generalized Epilepsies are one of its four major groups emerging from a double dichotomy of generalized versus localization-related and idiopathic versus symptomatic. The inclusion of biologic aspects such as syndrome-specific ages of onset ("age-related syndromes") or syndrome-specific relations of seizure occurrence to the sleep,wake cycle ("Epilepsy with Grand Mal on Awaking") meant that the syndrome classification merged the more biological views of the German school with the more neurophysiological ones of the French. Apart from establishing a common international language concerning epilepsy, the International Classification of Epilepsies and Epileptic Syndromes became an important stimulator of research, especially concerning the idiopathic epilepsies. In particular, genetic and functional imaging investigations aim at a better understanding of these conditions. It is now understood that most idiopathic syndromes have a,sometimes complex,genetic background, but we are also becoming aware of the inappropriateness of the time-honored term "generalized" and part of our dichotomies. Both localization-related and "generalized" idiopathic epilepsies seem to share a principle of ictogenesis based on functional anatomic pathogenic networks, and we seem to move toward understanding them as functional system disorders of the brain. [source] Symptomatic Epilepsies Imitating Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Hirokazu Oguni Summary:, The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1,4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs. [source] Evidence-based Treatment of Idiopathic Generalized Epilepsies with Older Antiepileptic DrugsEPILEPSIA, Issue 2005Nikolas Hitiris Summary:, Older antiepileptic drugs continue to play a major role in the treatment of the idiopathic generalized epilepsies. Comparative studies of ethosuximide and valproate have demonstrated equivalence in the treatment of childhood absence epilepsy. Valproate can be regarded as the recommended first-line treatment for juvenile myoclonic epilepsy based on case series reports. Studies in patients with generalized tonic-clonic seizures have not separated out idiopathic from secondary generalized events. Treatment for the other idiopathic generalized epilepsy syndromes lacks evidence other than a few case reports and diverse expert opinion. Further randomized controlled trials of older antiepileptic drugs are recommended to solidify the evidence-based treatment of the idiopathic generalized epilepsies. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Biparental Inheritance in Idiopathic Generalized EpilepsyEPILEPSIA, Issue 10 2004An C. Jansen No abstract is available for this article. [source] Genetic Architecture of Idiopathic Generalized Epilepsy: Clinical Genetic Analysis of 55 Multiplex FamiliesEPILEPSIA, Issue 5 2004Carla Marini Summary: Purpose: In families with idiopathic generalized epilepsy (IGE), multiple IGE subsyndromes may occur. We performed a genetic study of IGE families to clarify the genetic relation of the IGE subsyndromes and to improve understanding of the mode(s) of inheritance. Methods: Clinical and genealogic data were obtained on probands with IGE and family members with a history of seizures. Families were grouped according to the probands' IGE subsyndrome: childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and IGE with tonic,clonic seizures only (IGE-TCS). The subsyndromes in the relatives were analyzed. Mutations in genes encoding ,1 and ,2 ,-aminobutyric acid (GABA)-receptor subunits, ,1 and ,1 sodium channel subunits, and the chloride channel CLC-2 were sought. Results: Fifty-five families were studied. 122 (13%) of 937 first- and second-degree relatives had seizures. Phenotypic concordance within families of CAE and JME probands was 28 and 27%, respectively. JAE and IGE-TCS families had a much lower concordance (10 and 13%), and in the JAE group, 31% of relatives had CAE. JME was rare among affected relatives of CAE and JAE probands and vice versa. Mothers were more frequently affected than fathers. No GABA-receptor or sodium or chloride channel gene mutations were identified. Conclusions: The clinical genetic analysis of this set of families suggests that CAE and JAE share a close genetic relation, whereas JME is a more distinct entity. Febrile seizures and epilepsy with unclassified tonic,clonic seizures were frequent in affected relatives of all IGE individuals, perhaps representing a nonspecific susceptibility to seizures. A maternal effect also was seen. Our findings are consistent with an oligogenic model of inheritance. [source] Health-related Quality of Life of People with Epilepsy Compared with a General Reference Population: A Tunisian StudyEPILEPSIA, Issue 7 2004Hela Mrabet Summary:,Purpose: The goal of the study was to assess the health-related quality of life (HRQOL) of persons with epilepsy (PWE) by using the short form survey 36 (SF-36), to compare it with that of a control group and to detect factors influencing it. Methods: We collected clinical and demographic data and information on health status by using the Arabic translation of the SF-36 questionnaire from two groups: (a) 120 PWE consulting our outpatient clinic during a period of 4 months, and (b) 110 Tunisian citizens, representative of the Tunisian general population, as a control group. Results: The mean age of PWE group was 32.74 years, and 45.5% were men. Idiopathic generalized epilepsies were observed in 44.5% of cases, and symptomatic partial epilepsies, in 30%. The most commonly prescribed drug was sodium valproate (VPA). For the SF-36, PWE had lower scores than the control group for only three subscales: general health perception, mental health, and social functioning. Seizure frequency, time since last seizure, and the antiepileptic drug (AED) side effects were the most important variables influencing the HRQOL among PWE. Seizure-free adults have HRQOL levels comparable to those of the control group. Sociodemographic variables had no influence on the SF-36 subscales. Conclusions: HRQOL is impaired in Tunisian PWE. The influencing factors identified in this study differ from the previously published data. Several possible reasons such as family support and cultural and religious beliefs are proposed to explain these cross-cultural differences. A larger study should be conducted to verify such findings. [source] Idiopathic generalized epilepsies: a follow-up study in a single-centerACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010E. Kharazmi Kharazmi E, Peltola M, Fallah M, Keränen T, Peltola J. Idiopathic generalized epilepsies: a follow-up study in a single-center. Acta Neurol Scand: 122: 196,201. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To characterize adult patients with idiopathic generalized epilepsies (IGEs) with precise evaluation and to assess factors related to refractoriness. Materials and methods,,, Hospital records of all our patients with IGEs (n = 128) were evaluated in 2005 and followed-up until 2008. Results,,, In 2005, 76% of patients were 1-year seizure-free. Seizure freedom increased to 82% during the 3-year follow-up. Seizure freedom was not significantly associated with age, age at diagnosis, epilepsy duration, exposure to inappropriate initial antiepileptic drug (AED), or delay time between starting initial AED and appropriate AED. Women constituted 78% of patients with merely provoked seizures. In 58% of women with recent seizure, one to two avoidable precipitating factors, such as lack of sleep, alcohol, and forgetting to take AED, were observed. In 2008, all patients with no medication, 91% of monotherapy patients, 60% of patients on two AED, and 14% of patients on three AED were seizure-free. Conclusions,,, Most of patients with IGEs can be successfully treated with monotherapy. Refractory seizures in some patients may be because of avoidable factors, especially in young women. [source] The management of idiopathic generalized epilepsiesACTA NEUROLOGICA SCANDINAVICA, Issue 2005S. R. Benbadis Idiopathic generalized epilepsies (IGEs) are a well defined group of epilepsies, with onset predominantly in childhood. Recent evidence suggests that IGEs may also be prevalent but under-diagnosed in adults. IGEs respond well to appropriate treatment and 80,90% of cases become fully controlled. However, correct identification of IGE and selection of a broad-spectrum antiepileptic drug (AED) is crucial if cases of ,pseudo-intractability' are to be avoided. Preliminary evidence suggests that some of the newer AEDs are broad spectrum and may offer advantages in the treatment of IGEs. There is strong evidence that childhood-, adolescent- and adult-onset IGEs share biologic determinants and are best viewed as a spectrum or continuum of conditions. The diagnosis of IGE, even as a group, is very important for proper management. [source] Association of idiopathic generalized epilepsy with polymorphisms in the neuronal nicotinic acetylcholine receptor subunitsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2007Cheng-Chun Lee Abstract Idiopathic generalized epilepsy (IGE) refers to a common group of epilepsies, and genetic factors play an important role in the pathogenesis of these disorders. Mutations in CHRNA4 and CHRNB2 are associated with some cases of familial epilepsies classified as autosomal-dominant nocturnal frontal lobe epilepsies. We aimed to evaluate whether polymorphisms of CHRNA4 and CHRNB2are associated with IGE. A total of 75 children with IGE and 80 normal control subjects were included in the study. Each genetic polymorphism was typed by polymerase chain reaction (PCR)-based restriction analysis. The genotypes and allelic frequencies of each polymorphism were compared between the IGE patients and controls. The results showed that genotype and allelic frequency for CHRNB2 did not differ significantly between the groups. However, the genotype proportion of the CHRNA4 (Ser543Ser) gene in both groups was significantly different (P<0.0001). The T allele frequency was significantly higher (P=0.0126) in patients with IGE compared to healthy controls. The odds ratio (OR) for developing IGE in individuals with the CHRNA4 (Ser543Ser)-T homozygote was 4.9 (95% confidence interval (CI), 1.71,14.04) compared to individuals with two copies of the CHRNA4 (Ser543Ser)-C allele. This study demonstrates that the CHRNA4 gene may be one of the susceptibility factors for IGE. J. Clin. Lab. Anal. 21:67,70, 2007. © 2007 Wiley-Liss, Inc. [source] Nonepileptic Disorders Imitating Generalized Idiopathic EpilepsiesEPILEPSIA, Issue 2005Natalio Fejerman Summary:, Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic,clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed in Table 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening events in infants, cyanotic and pallid breath-holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages. Table 1. Nonepileptic disorders imitating idiopathic generalized epilepsies [source] Symptomatic Epilepsies Imitating Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Hirokazu Oguni Summary:, The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1,4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs. [source] Evidence-based Treatment of Idiopathic Generalized Epilepsies with Older Antiepileptic DrugsEPILEPSIA, Issue 2005Nikolas Hitiris Summary:, Older antiepileptic drugs continue to play a major role in the treatment of the idiopathic generalized epilepsies. Comparative studies of ethosuximide and valproate have demonstrated equivalence in the treatment of childhood absence epilepsy. Valproate can be regarded as the recommended first-line treatment for juvenile myoclonic epilepsy based on case series reports. Studies in patients with generalized tonic-clonic seizures have not separated out idiopathic from secondary generalized events. Treatment for the other idiopathic generalized epilepsy syndromes lacks evidence other than a few case reports and diverse expert opinion. Further randomized controlled trials of older antiepileptic drugs are recommended to solidify the evidence-based treatment of the idiopathic generalized epilepsies. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Molecular analysis of the A322D mutation in the GABAA receptor ,1 -subunit causing juvenile myoclonic epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Klaus Krampfl Abstract Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies. Although the mode of inheritance is usually complex, mutations in single genes have been shown to cause the disease in some families with autosomal dominant inheritance. The first mutation in a multigeneration JME family has been recently found in the ,1 -subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D. We further characterized the functional consequences of this mutation by coexpressing ,1 -, ,2 - and ,2 -subunits in human embryonic kidney (HEK293) cells. By using an ultrafast application system, mutant receptors have shown reduced macroscopic current amplitudes at saturating GABA concentrations and a highly reduced affinity to GABA compared to the wild-type (WT). Dose,response curves for current amplitudes, activation kinetics, and GABA-dependent desensitization parameters showed a parallel shift towards 30- to 40-fold higher GABA concentrations. Both deactivation and resensitization kinetics were considerably accelerated in mutant channels. In addition, mutant receptors labelled with enhanced green fluorescent protein (EGFP) were not integrated in the cell membrane, in contrast to WT receptors. Therefore, the A322D mutation leads to a severe loss-of-function of the human GABAA receptor by several mechanisms, including reduced surface expression, reduced GABA-sensitivity, and accelerated deactivation. These molecular defects could decrease and shorten the resulting inhibitory postsynaptic currents (IPSCs) in vivo, which can induce a hyperexcitability of the postsynaptic membrane and explain the occurrence of epileptic seizures. [source] Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsiesAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2001Diana Sobetzko Abstract Alterations of glycine receptor ,1 and , subunit genes have been associated with hypertonic motor disorders in both mice and humans. Mutations in genes encoding other ligand- and voltage-gated ion channels have been identified in rare monogenic forms of idiopathic generalized epilepsies (IGE). We tested the hypothesis that allelic variants of the glycine receptor subunit genes, GLRA3 and GLRB, both localized on chromosome 4q, confer susceptibility to common subtypes of IGE. Mutation screening was carried out in index patients of 14 IGE families. No pathogenic mutation was found, but two intronic polymorphisms were detected in the GLRB gene, and four intronic, three exonic, and one 3,-UTR polymorphisms were identified for the GLRA3 gene. Subsequent screening for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistical difference between a group of sporadic IGE patients (n,=,104) and a control group (n,=,141). The genotype frequencies for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistically significant difference between IGE patients (n,=,104) and an ethnically matched control group (n,=,141). Thus, no association between IGE and alterations in GLRA3 or GLRB genes could be detected, indicating that both genes do not play a major causative role in the epileptogenesis of common IGE subtypes. Still, these novel single nucleotide polymorphisms may be useful markers for candidate gene analyses of other disorders. © 2001 Wiley-Liss, Inc. [source] Idiopathic generalized epilepsies: a follow-up study in a single-centerACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010E. Kharazmi Kharazmi E, Peltola M, Fallah M, Keränen T, Peltola J. Idiopathic generalized epilepsies: a follow-up study in a single-center. Acta Neurol Scand: 122: 196,201. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To characterize adult patients with idiopathic generalized epilepsies (IGEs) with precise evaluation and to assess factors related to refractoriness. Materials and methods,,, Hospital records of all our patients with IGEs (n = 128) were evaluated in 2005 and followed-up until 2008. Results,,, In 2005, 76% of patients were 1-year seizure-free. Seizure freedom increased to 82% during the 3-year follow-up. Seizure freedom was not significantly associated with age, age at diagnosis, epilepsy duration, exposure to inappropriate initial antiepileptic drug (AED), or delay time between starting initial AED and appropriate AED. Women constituted 78% of patients with merely provoked seizures. In 58% of women with recent seizure, one to two avoidable precipitating factors, such as lack of sleep, alcohol, and forgetting to take AED, were observed. In 2008, all patients with no medication, 91% of monotherapy patients, 60% of patients on two AED, and 14% of patients on three AED were seizure-free. Conclusions,,, Most of patients with IGEs can be successfully treated with monotherapy. Refractory seizures in some patients may be because of avoidable factors, especially in young women. [source] Role of valproate across the ages.ACTA NEUROLOGICA SCANDINAVICA, Issue 2006Treatment of epilepsy in adults A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability. [source] The management of idiopathic generalized epilepsiesACTA NEUROLOGICA SCANDINAVICA, Issue 2005S. R. Benbadis Idiopathic generalized epilepsies (IGEs) are a well defined group of epilepsies, with onset predominantly in childhood. Recent evidence suggests that IGEs may also be prevalent but under-diagnosed in adults. IGEs respond well to appropriate treatment and 80,90% of cases become fully controlled. However, correct identification of IGE and selection of a broad-spectrum antiepileptic drug (AED) is crucial if cases of ,pseudo-intractability' are to be avoided. Preliminary evidence suggests that some of the newer AEDs are broad spectrum and may offer advantages in the treatment of IGEs. There is strong evidence that childhood-, adolescent- and adult-onset IGEs share biologic determinants and are best viewed as a spectrum or continuum of conditions. The diagnosis of IGE, even as a group, is very important for proper management. [source] Topiramate overdose: A case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticusEPILEPSIA, Issue 6 2010Christian Brandt Summary We report the case of a 21-year-old man with idiopathic generalized epilepsy who ingested about 8,000 mg of topiramate (TPM) in a suicide attempt. On admission to the hospital he had a nonconvulsive status epilepticus and received 4 mg lorazepam i.v. He recovered rapidly despite an initial TPM concentration of 144.6 ,g/ml. To our knowledge, this is the first report of a patient who survived such a high TPM concentration. The case indicates that nonconvulsive status epilepticus could be a manifestation of TPM intoxication. [source] Valproate teratogenicity and epilepsy syndromeEPILEPSIA, Issue 12 2008Edward B. Bromfield Summary Maternal valproate (VPA) use is associated with a significant risk for congenital malformations in the exposed fetus. Since VPA is commonly used in epilepsy syndromes with a presumed genetic cause (idiopathic epilepsies), it is possible that maternal genetic background contributes to this outcome. We reviewed responses to telephone questionnaires and medical records, when available, of enrollees in the North American Antiepileptic Drug Pregnancy Registry, classifying reason for treatment as idiopathic generalized epilepsy (IGE), partial epilepsy (PE), nonclassifiable epilepsy (NCE), or not epilepsy (NE). Of 284 VPA-exposed pregnancies, 30 (11.0%) were associated with malformations: IGE = 15/126 (12%), PE = 4/28 (14%), NCE = 9/105 (9%), NE = 2/25 (8%) (p > 0.7 for all comparisons). There was a trend toward increased malformation risk with higher VPA doses (p = 0.07). VPA, and not the underlying genetic syndrome, seems to be associated with the elevated risk for malformations in the drug-exposed fetus. [source] Genetic Architecture of Idiopathic Generalized Epilepsy: Clinical Genetic Analysis of 55 Multiplex FamiliesEPILEPSIA, Issue 5 2004Carla Marini Summary: Purpose: In families with idiopathic generalized epilepsy (IGE), multiple IGE subsyndromes may occur. We performed a genetic study of IGE families to clarify the genetic relation of the IGE subsyndromes and to improve understanding of the mode(s) of inheritance. Methods: Clinical and genealogic data were obtained on probands with IGE and family members with a history of seizures. Families were grouped according to the probands' IGE subsyndrome: childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and IGE with tonic,clonic seizures only (IGE-TCS). The subsyndromes in the relatives were analyzed. Mutations in genes encoding ,1 and ,2 ,-aminobutyric acid (GABA)-receptor subunits, ,1 and ,1 sodium channel subunits, and the chloride channel CLC-2 were sought. Results: Fifty-five families were studied. 122 (13%) of 937 first- and second-degree relatives had seizures. Phenotypic concordance within families of CAE and JME probands was 28 and 27%, respectively. JAE and IGE-TCS families had a much lower concordance (10 and 13%), and in the JAE group, 31% of relatives had CAE. JME was rare among affected relatives of CAE and JAE probands and vice versa. Mothers were more frequently affected than fathers. No GABA-receptor or sodium or chloride channel gene mutations were identified. Conclusions: The clinical genetic analysis of this set of families suggests that CAE and JAE share a close genetic relation, whereas JME is a more distinct entity. Febrile seizures and epilepsy with unclassified tonic,clonic seizures were frequent in affected relatives of all IGE individuals, perhaps representing a nonspecific susceptibility to seizures. A maternal effect also was seen. Our findings are consistent with an oligogenic model of inheritance. [source] Polygenic Control of Idiopathic Generalized Epilepsy Phenotypes in the Genetic Absence Rats from Strasbourg (GAERS)EPILEPSIA, Issue 4 2004Gabrielle Rudolf Summary: Purpose: Generalized nonconvulsive absence seizures are characterized by the occurrence of synchronous and bilateral spike-and-wave discharges (SWDs) on electroencephalographic recordings, concomitant with behavioral arrest. The GAERS (genetic absence rats from Strasbourg) strain, a well-characterized inbred model for idiopathic generalized epilepsy, spontaneously develops EEG paroxysms that resemble those of typical absence seizures. The purpose of this study was to investigate the genetic control of SWD variables by using a combination of genetic analyses and electrophysiological measurements in an experimental cross derived from GAERS and Brown Norway (BN) rats. Methods: SWD subphenotypes were quantified on EEG recordings performed at both 3 and 6 months in a cohort of 118 GAERS × BN F2 animals. A genome-wide scan of the F2 progenies was carried out with 146 microsatellite markers that were used to test each marker locus for evidence of genetic linkage to the SWD quantitative traits. Results: We identified three quantitative trait loci (QTLs) in chromosomes 4, 7, and 8 controlling specific SWD variables in the cross, including frequency, amplitude, and severity of SWDs. Age was a major factor influencing the detection of genetic linkage to the various components of the SWDs. Conclusions: The identification of these QTLs demonstrates the polygenic control of SWDs in the GAERS strain. Genetic linkages to specific SWD features underline the complex mechanisms contributing to SWD development in idiopathic generalized epilepsy. [source] Photosensitivity in Relation to Epileptic Syndromes: A Survey from an Epilepsy Center in JapanEPILEPSIA, Issue 3 2001Hideaki Shiraishi Summary: ,Purpose: We examined the incidence and distribution of photosensitivity among the different age groups and different types of epilepsies and epileptic syndromes. Furthermore, we considered the influence of ethnic and geographic factors on the incidence of photoparoxysmal response (PPR) in epilepsy patients. Methods: We analyzed the responses to intermittent photic stimulation (IPS) by using a Grass PS22 or PS33 photic stimulator for in 2,187 unselected patients with epilepsy who were treated in our center. Results: The classic PPR was elicited in 37 (1.7%) patients. The mean age of these 37 patients was 17.0 years. The subpopulation of patients having PPR included 2.0% of all patients with symptomatic generalized epilepsy, 5.6% (p < 0.01) of those with idiopathic generalized epilepsy, 0.7% of those with symptomatic localization-related epilepsy, and 2.9% of those with undetermined epilepsy. PPR accounted for 17.4 % (p < 0.01) of the patients with juvenile myoclonic epilepsy, 7.6% (p < 0.01) of those with grand mal on awakening, and 6.1% (p < 0.01) of those with symptomatic occipital lobe epilepsy. The incidence of PPR increased in patients up to age 15 years, and suddenly decreased after age 20 years. Conclusion: The present study presents the first report from eastern Asia, analyzing the incidence of PPR with a restricted definition comparable to the other studies, and the rate of PPR was relatively low compared with the studies performed in the European countries. We could confirm the clear relation between age and positive PPR. [source] Association of idiopathic generalized epilepsy with polymorphisms in the neuronal nicotinic acetylcholine receptor subunitsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2007Cheng-Chun Lee Abstract Idiopathic generalized epilepsy (IGE) refers to a common group of epilepsies, and genetic factors play an important role in the pathogenesis of these disorders. Mutations in CHRNA4 and CHRNB2 are associated with some cases of familial epilepsies classified as autosomal-dominant nocturnal frontal lobe epilepsies. We aimed to evaluate whether polymorphisms of CHRNA4 and CHRNB2are associated with IGE. A total of 75 children with IGE and 80 normal control subjects were included in the study. Each genetic polymorphism was typed by polymerase chain reaction (PCR)-based restriction analysis. The genotypes and allelic frequencies of each polymorphism were compared between the IGE patients and controls. The results showed that genotype and allelic frequency for CHRNB2 did not differ significantly between the groups. However, the genotype proportion of the CHRNA4 (Ser543Ser) gene in both groups was significantly different (P<0.0001). The T allele frequency was significantly higher (P=0.0126) in patients with IGE compared to healthy controls. The odds ratio (OR) for developing IGE in individuals with the CHRNA4 (Ser543Ser)-T homozygote was 4.9 (95% confidence interval (CI), 1.71,14.04) compared to individuals with two copies of the CHRNA4 (Ser543Ser)-C allele. This study demonstrates that the CHRNA4 gene may be one of the susceptibility factors for IGE. J. Clin. Lab. Anal. 21:67,70, 2007. © 2007 Wiley-Liss, Inc. [source] Predicting seizure control: Cortical excitability and antiepileptic medicationANNALS OF NEUROLOGY, Issue 1 2010Radwa A. B. Badawy MBBCh Objective Approximately 30% of patients with newly diagnosed epilepsy do not respond to antiepileptic drugs (AEDs), but this is not predictable. We used transcranial magnetic stimulation to determine the effect of AEDs on cortical excitability in patients with epilepsy and correlated this with a successful response to treatment. Methods Ninety-nine drug-naïve patients with newly diagnosed epilepsy (55 idiopathic generalized epilepsy, 44 focal epilepsy) were evaluated. Motor threshold and cortical excitability on recovery curve analysis were measured before and 4 to 16 weeks after starting medication. After 1 year of treatment, 43 of 55 idiopathic generalized epilepsy and 26 of 44 focal epilepsy patients were seizure free. Results A decrease in cortical excitability occurred in the seizure-free group as indicated by an increase in motor threshold (p < 0.05) and intracortical inhibition on recovery curve analysis, maximum at the 250-millisecond interstimulus interval (p < 0.01) compared with pretreatment values. These changes were not present in the group with ongoing seizures. Interpretation Seizure freedom is marked by a reduction in transcranial magnetic stimulation measures of cortical excitability, evident shortly after beginning therapy. This virtual normalization of cortical excitability occurred regardless of the seizure characteristics or AED used. Failure to show this response to AED treatment may be valuable as an early predictor of pharmacoresistance in individual patients. ANN NEUROL 2010;67:64,73 [source] Valproate in children with newly diagnosed idiopathic generalized epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010K. D. Holland Holland KD, Monahan S, Morita D, Vartzelis G, Glauser TA. Valproate in children with newly diagnosed idiopathic generalized epilepsy. Acta Neurol Scand: 2010: 121: 149,153. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, Sparse information on dose,response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available. The aim of this study is to characterize the therapeutic dose of valproate in children with newly diagnosed IGE. Materials and methods,,, Effect of initial valproate monotherapy and doses associated with seizure freedom were examined in consecutive children with IGE identified from a New Onset Seizure Clinic. Results,,, Of 84 patients identified, 48 (57%) became seizure-free on valproate monotherapy and another 10 patients became seizure-free but discontinued VPA because of adverse effects. The mean dose in seizure-free children was 15.7 mg/kg/day and over 95% of IGE patients will respond below 25 mg/kg/day. Conclusions,,, Half of children became seizure-free on valproate monotherapy and did so at modest doses. [source] Opinion of Belgian neurologists on antiepileptic drug treatment in 2006: Belgian study on epilepsy treatment (BESET-2)ACTA NEUROLOGICA SCANDINAVICA, Issue 6 2009B. Legros Objectives,,, (i) To describe the medical treatment of epilepsy in Belgium in 2006, (ii) to detect the presence or absence of consensus in epilepsy treatment and (iii) to analyze the evolution of the neurologists' opinion between 2003 and 2006. Materials and methods,,, In December 2006, 100 neurologists were interviewed with a structured questionnaire, based on ordinal four-point scales. The questionnaire contained questions on treatment choices in adult patients with epilepsy. The results of this survey were compared with results of a previous one done in 2003. Results,,, Initial monotherapy was the preferred treatment strategy. Valproate was first choice in idiopathic generalized epilepsy. Carbamazepine and oxcarbazepine were first choice in focal epilepsy with partial seizures. Valproate was also first choice in focal epilepsy with secondarily generalized seizures. New antiepileptic drugs were recommended in second line. However, in special treatment situations, they were considered first-line, e.g. lamotrigine in case of women in childbearing age. In comparison with 2003, there was a trend of using earlier the new antiepileptic drugs. Conclusions,,, In end 2006, carbamazepine, valproate and oxcarbazepine were considered to be first choice drugs, whereas other newer drugs, like lamotrigine, levetiracetam and topiramate were predominantly prescribed in second line. [source] |